Dr. Buynak has recently developed synthetic methodology leading to the preparation of the previously unknown 6-vinylidenepenams and has prepared several compounds which exhibit potent biological activity. Inhibitors of cephalosporinase and of elastase have been discovered. b-- Lactamase inhibitors are used in treating the rapidly proliferating number of penicillin-resistant strains of bacterial infection. Leukocyte elastase is overactive in patients with emphysema and in those with rheumatoid arthritis. A mechanistic study of these inhibitors is proposed. A synthetic investigation will determine the nature and stereochemistry of allenyl substituents necessary for optimal biological activity. Derivatives which can penetrate the cell wall will be prepared. Terminal (aminoalkyl)vinylidene derivatives are proposed as targets which fulfill these criteria. Cephalosporin analogs of the allenes will be prepared. The cephalosporin skeleton win convey additional stability and the relatively flat topography of the skeleton will broaden the scope of enzymes which are susceptible to inhibition. New inhibitors, involving elemental substitution of the penam nucleus, will be prepared. These materials will help define the lactamase mechanism. In a synthetic investigation, new intramolecular addition reactions of allenes will be explored. These reactions are expected to generate theoretically important trimethylenemethanes as intermediates. Metal-stabilized trimethylenemethanes will be prepared from the corresponding carbenoids to determine their synthetic utility.